Antiplatelet therapy in patients with Covid-19: A retrospective observational study.

Introduction: Covid-19 is associated with a high risk of venous thromboembolism. In addition, cases of arterial thromboembolism were also reported. We investigated the effect of antiplatelet therapy on the disease course. Methods: We evaluated a cohort of inpatients with Covid-19 (n â€‹= â€‹152). We recorded the patient's demographic data, their comorbidities, medication use including the use of antiplatelets and anticoagulants, laboratory findings and data about mechanical ventilation. We then separated the patient's outcomes into either being "bad" (dead or referral to higher level of care) or "good" (discharged). Then we evaluated the factors that contributed to the patient needing ventilatory support and to showing typical radiological findings. Results: In our cohort, 21 patients received ventilatory support whereas 131 did not require the use of ventilators. 127 patients had good outcomes and 25 had bad outcomes. By using multivariate analysis, we found that the need for ventilatory support was the strongest predictor of a bad outcome. All patients who were on ventilators displayed typical radiological findings. The factors predicting the need for ventilatory support were LDH and CRP levels, the presence of cardiac conduction abnormalities as well as chronic lung conditions. Cardiac conduction abnormalities, LDH and CRP levels, and the use of antiplatelets, were factors that predicted typical radiological findings. Conclusions: There was a higher incidence of typical radiological findings in patients on antiplatelet medication. However, it did not translate into changes in the ventilation requirement or in the outcome. The need for mechanical ventilation was the strongest predictor of a bad outcome.

Unclear abdominal discomfort: pivotal role of carbohydrate malabsorption.

BACKGROUND/AIMS: Carbohydrate malabsorption is frequent in patients with functional gastrointestinal disorders and in healthy volunteers and can cause gastrointestinal symptoms mimicking irritable bowel syndrome (IBS). The aim of this study was to investigate the prevalence of symptomatic lactose and fructose malabsorption in a large population of patients with IBS-like symptoms based on Rome II criteria. METHODS: Patients with unclear abdominal discomfort (n = 2,390) underwent lactose (50 g) and fructose (50 g) hydrogen (H2) breath tests and depending on the results further testing with 25 g fructose or 50 g glucose, or upper endoscopy with duodenal biopsies. Additionally, this population was investigated regarding the prevalence of small intestinal bacterial overgrowth (SIBO) based on glucose breath test and celiac disease. RESULTS: Of the 2,390 patients with IBS-like symptoms, 848 (35%) were symptomatic lactose malabsorbers and 1,531 (64%) sympto-matic fructose malabsorbers. A combined symptomatic carbohydrate malabsorption was found in 587 (25%) patients. Severe fructose malabsorbers (pathologic 25 g fructose test) exhaled significantly higher H2 concentrations in the 50 g test than pa-tients with negative 25 g fructose test (P < 0.001). Out of 460/659 patients with early significant H2 increase in the lactose and fructose test who underwent a glucose breath test, 88 patients had positive results indicative of SIBO and they were sig-nificantly older than patients with negative test result (P < 0.01). Celiac disease was found in 1/161 patients by upper endoscopy. CONCLUSIONS: Carbohydrate malabsorption is a frequent but underestimated condition in patients with IBS-like symptoms although diagnosis can be easily confirmed by H2 breath testing.

Serotonin transporter activity and serotonin concentration in platelets of patients with irritable bowel syndrome: effect of gender.

BACKGROUND: In the past decade, a strong argument has been built for the role of serotonin (5HT) and the serotonin transporter (SERT) in irritable bowel syndrome (IBS). However, it is still not clear how SERT contributes to this clinically heterogeneous disease. The present study addressed this issue by implementing platelet (plt) markers of SERT activity in the assessment protocol. METHODS: Fasting blood samples of 149 (51 male/98 female) subjects with Rome II and III defined IBS subtypes, and 163 healthy control subjects (CSs; 75 male/88 female) were analyzed for platelet 5HT concentration and 5HT uptake activity [maximum uptake rate (V (max)) and affinity constant (K (m))]. RESULTS: Gender had a significant impact on platelet markers of SERT activity. Male IBS patients showed significantly lower median V (max) and K (m) values than the male CS (V (max) 1.706 vs. 2.148 nmol/10(9) plts x min, P < 0.001; K (m) 346 vs. 410 nmol, P = 0.008) without any significant reduction in platelet 5HT concentration (362 vs. 394 ng/10(9) plts). On the other hand, V (max) values were not different between female IBS patients and female CS (1.642 vs. 1.741 nmol/10(9) plts x min), but platelet 5HT concentration was significantly lower in females with diarrhea-predominant IBS (363 vs. 435 ng/10(9) plts, P < 0.05). CONCLUSION: Although an absolute extrapolation from platelets to the gastrointestinal tissue does not appear to be justified, our findings demonstrated that the contribution of disturbed SERT activity to IBS is not uniform and is possibly gender-specific. The results suggest that an assessment of SERT function in platelets may help to elucidate the differences between IBS patients in response to drugs affecting the 5HT system.

Subjective theories of illness and clinical and psychological outcomes in patients with irritable bowel syndrome.

OBJECTIVES: Patients' ideas about the nature, cause, and treatment of their illnesses are part of the complex process of coping with illness. To date, limited research on subjective theories of illness in patients with irritable bowel syndrome (IBS) has been performed. The aim of the study was to investigate patients' subjective theories of illness and how these are related to clinical and psychological outcome criteria, in particular IBS symptom severity and quality of life. METHODS: Eighty-eight patients with IBS, as defined by Rome III criteria, were administered a battery of questionnaires to collect the following data: sociodemographic variables, subjective theories of illness (Subjektive Krankheitstheorien, Cause Questionnaire), anxiety (Hospital Anxiety and Depression Scale), depression (Beck Depression Inventory), quality of life (SF-12), and IBS symptoms (Questionnaire for Gastrointestinal Symptoms). RESULTS: Almost all patients reported theories of illness reflecting their subjective causal assumptions. The most frequently mentioned causal factors were physical illness, intrapsychic factors, and stress. Patients with mainly somatic attributions had higher IBS symptoms scores (P<.05) and reduced physical quality of life. Intrapsychic attributions were associated with reduced mental quality of life and enhanced physical quality of life (P<.01). All correlations were independent of gender, age, and irritable bowel subgroups. CONCLUSIONS: Subjective theories of illness can have significant implications for IBS symptom severity, as well as for physical and mental quality of life.

First evidence for an association of a functional variant in the microRNA-510 target site of the serotonin receptor-type 3E gene with diarrhea predominant irritable bowel syndrome.

Diarrhea predominant irritable bowel syndrome (IBS-D) is a complex disorder related to dysfunctions in the serotonergic system. As cis-regulatory variants can play a role in the etiology of complex conditions, we investigated the untranslated regions (UTRs) of the serotonin receptor type 3 subunit genes HTR3A and HTR3E. Mutation analysis was carried out in a pilot sample of 200 IBS patients and 100 healthy controls from the UK. The novel HTR3E 3'-UTR variant c.*76G>A (rs62625044) was associated with female IBS-D (P = 0.033, OR = 8.53). This association was confirmed in a replication study, including 119 IBS-D patients and 195 controls from Germany (P = 0.0046, OR = 4.92). Pooled analysis resulted in a highly significant association of c.*76G>A with female IBS-D (P = 0.0002, OR = 5.39). In a reporter assay, c.*76G>A affected binding of miR-510 to the HTR3E 3'-UTR and caused elevated luciferase expression. HTR3E and miR-510 co-localize in enterocytes of the gut epithelium as shown by in situ hybridization and RT-PCR. This is the first example indicating micro RNA-related expression regulation of a serotonin receptor gene with a cis-regulatory variant affecting this regulation and appearing to be associated with female IBS-D.

Somatic comorbidities of irritable bowel syndrome: a systematic analysis.

OBJECTIVE: A large number of irritable bowel syndrome (IBS) patients are additionally afflicted with other somatic intestinal and/or extraintestinal comorbidities. The occurrence of one or more comorbidities is correlated with enhanced medical help seeking, worse prognosis, and higher rates of anxiety and depression-all resulting in a reduced quality of life. The aims of this study were, firstly, to review the literature on comorbidities of IBS and to assess gastrointestinal and extraintestinal comorbidities, and, secondly, to evaluate explanatory hypotheses and possible common pathophysiological mechanisms. METHODS: We systematically reviewed the scientific literature in the past 25 years, as cited in MEDLINE. RESULTS: IBS patients present with a twofold increase in somatic comorbidities compared to controls, possibly caused by common pathophysiological mechanisms. Nevertheless, to date, there has been no convincing evidence for a consolidated underlying pathophysiology or somatization. Gastrointestinal disorders, such as functional dyspepsia, gastroesophageal reflux disease, functional constipation, and anal incontinence, occur in almost half of the patients. In a broad variety of extraintestinal comorbidities, fibromyalgia, chronic fatigue syndrome, and chronic pelvic pain are best documented and appear in up to 65%. CONCLUSION: The knowledge and structured assessment of comorbid somatic symptoms might allow to identify subgroups of IBS patients with special characteristics and lead to adaptation of the therapeutic concept.

Peripheral injection of CCK-8S induces Fos expression in the dorsomedial hypothalamic nucleus in rats.

Peripheral cholecystokinin (CCK) plays a physiological role in the regulation of food intake. The dorsomedial hypothalamic nucleus (DMH) has been implicated in the brain regulation of food intake and satiety. The aim of this study was to determine if peripherally administered CCK affects neuronal activity in the DMH, as assessed by Fos expression. Density of Fos-positive neurons was determined in the DMH, paraventricular nucleus of the hypothalamus (PVN), arcuate nucleus of the hypothalamus (ARC) and ventromedial hypothalamic nucleus (VMH) in non-fasted Sprague-Dawley rats in response to intraperitoneally (ip) injection of CCK-8S (2 microg/kg, n=6) or vehicle (0.15 M NaCl; n=6). CCK-8S increased Fos immunoreactivity in the DMH (mean+/-SEM; cells/section: 108+/-10 versus 54+/-6, p<0.001) and PVN (120+/-12 versus 20+/-3, p<0.001) compared to the vehicle group while not influencing Fos expression in the ARC and VMH. Double labeling showed that 27.4+/-6.4% (n=3) of Fos-positive neurons induced by CCK-8S were positive for corticotropin-releasing factor immunoreactivity, that were mainly localized in the ventral part of the DMH, and encircled in a network of tyrosine-hydroxylase-immunoreactive positive fibers. These data indicate that in addition of the PVN, peripheral CCK increases neuronal activity in the DMH suggesting a possible role in this hypothalamic nucleus in the satiating effect of the peptide.

Emotional stress reactivity in irritable bowel syndrome.

OBJECTIVES: Irritable bowel syndrome (IBS) has been proposed to be a stress-related disorder. Research on stress reactivity in IBS has yielded ambiguous results, regarding responses to physical and mental stress. This study aimed to investigate the responses to emotional stress in IBS patients. METHODS: Twelve IBS patients and 12 healthy individuals underwent public speaking anticipation as an emotional stressor and a control situation. Stress reactivity was quantified by subjective and psychophysiological measures. RESULTS: Stress responses were elicited in healthy controls and IBS patients. Differential stress responses were observed in measurements of heart rate. There was no change in rectal sensitivity under stress, whereas patients exhibited lower discomfort thresholds than healthy controls in all conditions. CONCLUSION: This study measured reactivity to an emotional stressor in IBS. It provides evidence that there is a specific alteration of stress responses in IBS patients, but no overall exaggerated stress response. IBS patients showed a broader and less specific response to emotional stress than healthy controls. Rectal sensitivity was unchanged under emotional stress both in IBS patients and healthy controls.

Cerebral processing of auditory stimuli in patients with irritable bowel syndrome.

AIM: To determine by brain functional magnetic resonance imaging (fMRI) whether cerebral processing of non-visceral stimuli is altered in irritable bowel syndrome (IBS) patients compared with healthy subjects. To circumvent spinal viscerosomatic convergence mechanisms, we used auditory stimulation, and to identify a possible influence of psychological factors the stimuli differed in their emotional quality. METHODS: In 8 IBS patients and 8 controls, fMRI measurements were performed using a block design of 4 auditory stimuli of different emotional quality (pleasant sounds of chimes, unpleasant peep (2000 Hz), neutral words, and emotional words). A gradient echo T2*-weighted sequence was used for the functional scans. Statistical maps were constructed using the general linear model. RESULTS: To emotional auditory stimuli, IBS patients relative to controls responded with stronger deactivations in a greater variety of emotional processing regions, while the response patterns, unlike in controls, did not differentiate between distressing or pleasant sounds. To neutral auditory stimuli, by contrast, only IBS patients responded with large significant activations. CONCLUSION: Altered cerebral response patterns to auditory stimuli in emotional stimulus-processing regions suggest that altered sensory processing in IBS may not be specific for visceral sensation, but might reflect generalized changes in emotional sensitivity and affective reactivity, possibly associated with the psychological comorbidity often found in IBS patients.

Bombesin, but not amylin, blocks the orexigenic effect of peripheral ghrelin.

The interaction between ghrelin and bombesin or amylin administered intraperitoneally on food intake and brain neuronal activity was assessed by Fos-like immunoreactivity (FLI) in nonfasted rats. Ghrelin (13 microg/kg ip) increased food intake compared with the vehicle group when measured at 30 min (g/kg: 3.66 +/- 0.80 vs. 1.68 +/- 0.42, P < 0.0087). Bombesin (8 microg/kg) injected intraperitoneally with ghrelin (13 microg/kg) blocked the orexigenic effect of ghrelin (1.18 +/- 0.41 g/kg, P < 0.0002). Bombesin alone (4 and 8 microg/kg ip) exerted a dose-related nonsignificant reduction of food intake (g/kg: 1.08 +/- 0.44, P > 0.45 and 0.55 +/- 0.34, P > 0.16, respectively). By contrast, ghrelin-induced stimulation of food intake (g/kg: 3.96 +/- 0.56 g/kg vs. vehicle 0.82 +/- 0.59, P < 0.004) was not altered by amylin (1 and 5 microg/kg ip) (g/kg: 4.37 +/- 1.12, P > 0.69, and 3.01 +/- 0.78, respectively, P > 0.37). Ghrelin increased the number of FLI-positive neurons/section in the arcuate nucleus (ARC) compared with vehicle (median: 42 vs. 19, P < 0.008). Bombesin alone (4 and 8 microg/kg ip) did not induce FLI neurons in the paraventricular nucleus of the hypothalamus (PVN) and coadministered with ghrelin did not alter ghrelin-induced FLI in the ARC. However, bombesin (8 microg/kg) with ghrelin significantly increased neuronal activity in the PVN approximately threefold compared with vehicle and approximately 1.5-fold compared with the ghrelin group. Bombesin (8 microg/kg) with ghrelin injected intraperitoneally induced Fos expression in 22.4 +/- 0.8% of CRF-immunoreactive neurons in the PVN. These results suggest that peripheral bombesin, unlike amylin, inhibits peripheral ghrelin induced food intake and enhances activation of CRF neurons in the PVN.

Megacolon in adulthood after surgical treatment of Hirschsprung's disease in early childhood.

Hirschsprung's disease (HD) is a disorder associated with congenital malformation of the enteric nervous system with segmental aganglionosis. Prevailing therapy includes a resection of the affected part of the bowel. However, patients often do not obtain complete functional improvement after surgical treatment. We present the case of a 25-year-old woman who had surgical treatment of HD in early childhood. After that procedure she had clinical features of constipation for years in the end, passing of stool once a week, requiring laxatives and enemas. We diagnosed an incomplete resection of the aganglionic bowel via rectal biopsy and resected the remaining aganglionic segment. Two months after surgery the patient's bowel function improved to a frequency of 1-4 stools per day. We conclude that regular follow-up is required to identify HD patients with persistent alterations of bowel function after surgery. In patients presenting with constipation, recognition of a remaining aganglionic segment or other alterations of the enteric nervous system should be aimed at in an early stage.